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12/5/2014 ARBOVIRUSES LECT # 30

  • FIRST OF ALL ,HOW TO CLASSIFY THE VIRUSES ???

-VIRUSES are classified depending on many aspects like:

  1. DNA or RNA viruses
  2. Enveloped or not
  3. Site of infection
  4. Host (animal, plant ,zoonosis)
  5. Structure of virus itself

*we are going to talk mainly about these viruses that are mainly cause diseases in human and animals

*one of the main important characteristics of these viruses that in their host ,in their original host ,generally they cause disease ,tumor. while if they are transmitted to a non-original host .they can cause a very severe disease and sometimes a killing disease .

  • So viruses in their host ….cause disease and some certain tumors .
  • In the other non-original host…cause severe or killing disease

-We will talk about these arboviruses which they are large groups :

  1. Etiology
  2. Epidemiology and history
  3. Pathogenesis and pathology
  4. Clinical manifestation
  5. Diagnosis
  6. Treatment
  7. Prevention and controls

This group of viruses is a very very large group ,the name is taken from different words

ARBO-VIRUSES :

AR: arthropod, which they are vectors ,which transmits the disease from human to animal and vis versa

B: born viruses

  • Arthropod born viruses : which means viruses are transmitted by these arthropod
  • Generally they are more than 600 different viruses and transmitted by arthropod vectors

*the definition of WHO of these viruses:

-viruses maintained in nature principally or to important extent through biological transmission between susceptible vertebrate hosts by :

Hematophagus arthropod

Trans-ovarial transmission

Venereal –transmission

In arthropods .

Sometimes ,these viruses will be transmitted from arthropods + from the ovas to the human or others .

These viruses we can see them mainly in 3-families :

1)Toga-viruses

2)Bunya –viruses

3)Flavi-viruses

*each one has many types of viruses .for example togaviruses…they mainly cause encephalitis in animals ,,,examples: EEE: east equine encephalitis

WEE: west equine encephalitis

VEE: venezuelen equine encephalitis

**equine : means horse ,which means ,they can cause encephalitis mainly in horse

  • Bunya-viruses , they can cause hemorrhagic fever ,rift-valley fever ,sand-fly fever

Crimean –congo hemorrhagic fever(Cuz the arthropod can transmit these types of diseases ).

  • Flavi-viruses: causes :- fever :yellow/dengue

-encephalitis(Japanese)

  • The main characteristics of togaviridae :

-sindbis …they are transmitted +they are found mainly in the forest which there are a high rain +humidity

-VEE

-EEE

-WEE

  • Flavi-viruses:

*mainly they are :

1)Dangue fever

2)Yellow fever

3)Japanese encephalitis

4)West-nile encephalitis

5)Sant. louis encephalitis

6)Russian spring-summer encephalitis

7)Powassan encephalitis

*these viruses are enveloped ,they are icosa-hedral

If we look to the toga-viridae + flavi-viridae…..they are heat +detergent labile (cuz they are enveloped ,the envelop is sensitive to heat + to the detergent (ether,alcohol)

They are icsahedral : size:40-75 nm for toga /40-45nm for flavi

Genome:is +ve ,ssRNA ,directly give m-RNA

  • Bunya-viridae : again :they are heat +detergent labile because of the envelope
  • Helical in shape
  • (-ve)ssRNA +segmented …this means it should develop a (+ve) strand inorder to be able to give m-RNA
  • Reo-viridae : *no envelope ,so resistance to the heat and detergent

*ds-RNA +segmented

*icosahedralcapsid shape

So the virus structure has 3-types of proteins

It has three proteins

Envelope protein

Core protein

Membrane protein : which they sever as antigenic characteristic for the virus which can invade the immune response or we can prepare the vaccine against these virus.

General Antigenic Properties of Flaviviral Proteins - 1

E-glycoprotein

Most important flaviviral antigen

Very immunogenic

Most serological assays detect reactivity with this protein

So we use glycoprotein to diagnosis this group

Capsid

Elicits primarily group-reactive antibody,it is not specific to ward this strain

M-protein

Very small (75 a.a.)

Embedded in the virion envelope membrane and not highly immunogenic

How these viruses replicate

The replication mainly if there is a receptor on the cell membrane (envelope ),the structure of envelope protein is lipoproteins belong to the host cell so generally it is part of host cell.

1st step there will be a reaction of that virus to their receptor on the host cell and the lipid layer will be assochaited/dissochation with the cell membrane of the host cell then it will enter to the cell

2nd step : after that , the virus will be uncapside by proteolytic enzyme ,the RNA will be released from there ,if it is( +ve) then it start to produce the proteins in Golgi apparatus ,ER of the host cell

3rd step :then all the component of virus after formation will be associated in to the capside

4th step :

Then they bud- out the cell ((the cell will note be destroyed, instead of that there will be budding)) so these viruses will bud out the host cell ,they will take from cell membrane (lipo-protein )

Transmission

Japanese encephalitis, dengue, yellow fever, St. Louis encephalitis, EEE, WEE, VEE etc / Mosquitoes
Crimean-Congo haemorrhagic fever, various tick-borne encephalitides etc. / Ticks
Sicilian sandfly fever, Rift valley fever. / Sandflies

Animal Reservoirs

Japanese encephalitis, St Louis encephalitis, EEE, WEE / Birds
Japanese encephalitis / Pigs
Yellow Fever / Monkeys
VEE, Russian Spring-Summer encephalitis / Rodents

Transmission of theReservoirs

The most common route of infection is the bite of infectious mosquito it will take blood from the animals or from human and it well be transmitted to other reservoirs.

Other transmission modes where revealed in 2002 such as:

1)Blood Transfusion 2),Organ Transplantation3), Intrauterine 4) ,Percutaneous exposure (occ. exposure), 5)Breast milk (probable)

Transmission Cycles

e.g. dengue, urban yellow fever.
Reservoir may be in either man or arthropod vector.
In the latter trans-ovarial transmission may take place(from vector to its ova then to human) / / *Man - arthropod –man(no animal INTERFERE)
e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.
The reservoir is in ananimal.
The virus is maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected incidentally.
Both cycles may be seen with some arboviruses such as yellow fever. / / *Animal - arthropod vector - man (Human not the main person who get the infection)

Epidemiologic Feature

The major outbreaks coincided with the heavy rainfall or floods.

Seasonal: more common in summer, July to October

Infection provides lifelong immunity cause of lipoprotein and capsidevery strong immunogenic protein or if u give vaccine the person will be immune..

Worldwide distribution

More than 530 species, 150 pathogen to man

Pathogenesis

The nature of flavi-virus disease is determined primarily by:

The specific tropisms of the individual virus type( could cause fever ,hemorrhagic ,encephalitis)dpend on which virus we talking about to see the pathogen

The concentration of infecting virus: how much virus enter the body (few amount or large amount )

Individual host response to the infection: good ,compromised have other disease)

/ Generally , when the arthropode suck blood ,it gives the virus to human
Generally withen 2-3 days no signs & symptom will be just itching at the bit site
After 3-7 day the virus will go to the blood so cause viremia
When it cause viremia it can go to the liver and to the lymphocytes (it cause mild systemic disease ,fever ,common flue ,chills )
After one week or more we can see that there is production of Ab in the blood .
If there is enough Ab no more symptom
if there is no enough Ab or immune compromised so the virus can go to brain and cause encephalitis ,yellow fever ,hepatitis ,hemorrhagic fever
summery :
virus from bite site …go to macrophage –blood circulation…2 possibility
1)enough Ab …no secondary invasion ..mild symptom
2)no enough Ab secondary invasion ..sever symptom

Clinical picture / 4 stage

A Prodromal Stage

An Acute encephalitic Stage

The Convalescence Stage

A Sequela Stage …then death of the patient

Pathogenesis and immunity

Beside viral receptor, virus may attach to Fc receptor (receptor found on the surface of macrophages and monocytes) via Ab to result in an increase of virus infection.(virus entry to inside the cell)

Antibody is produced to block infection, so if we have good a mount of Ab's to have a neutralization rxn( (binding of the virus with Ab ,so the virus will not be able to bind to the host cell)) However, non-neutralizing Ab may have antibody dependent enhancement (ADE) effect to enhance virus replication by hundred folds.

Arthropod-Borne Viruses

a) Dengue fever b) Yellow fever C)chikungunya

signs and symptom

Fever/Rash/Arthritis

Triad of fever/rash/arthritis

Symptoms generally appear after 2-3 days incubation

a) fever, chills, myalgia

b) polyarthralgia mainly affecting small joint

c) maculopapular rash

Arthritis generally resolves in a few weeks, but may persist for months, or years in some cases.

Encephalitis

Don’t remember the name in the slide 

In Encephalitis we need a vector ,a reservoir (animal ), u need human

Vector transmitted virus from animal to human (host )

West Nile Virus

/ Geographic distribution:
Africa, Middle East, Western Asia, Europe, Australia, North America, Central America / Principal arthropod vector – mosquitoes / Primary host – wild birds / Flavivirus

It causes encephalitis which has Case-fatality rates average 10 – 20 % (higher in elderly).death orSurvivors may be left with permanent neurologic sequelae such as mental retardation, epilepsy, paralysis, deafness, and blindness.

Diagnosis:-

++ material of epdimology :we take it from human ,vector ,suspected animal

Laboratory Tests++

*Tentative diagnosis

*Antibody titer:we can use serelogical exam to look for Ab titer

*JE-specific IgM in serum or CSF in encephalitis

*Definitive diagnosis if we can isolate the virus

*Virus isolation: Blood, CSF sample, brain

So we can do:

1) serological exam

2)culture

3) direct detection test:- by doing molecular biology to look for RNA of the specimen or direct detection of Ag in the infected cells (virus enter macrophage and make new antigenicity to the cell so we make direct to look for new Ag .

Prevention:

Because the vector are the main things if we can protect our self from the vector this mean we can prevent the transmition

Method for prevention :

Surveillance - of disease and vector populations( the first thing they do in malaria prevention is killing the mosquito in order to get ride off the disease '

Control of vector - pesticides, elimination of breeding grounds

Personal protection - screening of houses, bed nets, insect repellants

Vaccination - available for a number of arboviral infections e.g. Yellow fever, Japanese encephalitis, Russian tick-borne encephalitis

Treatment/Vaccines/Control measures:

A. Encephalitis

1. Vaccines exist for a number of these viruses, but are used mainly for horses, at risk lab workers, and some fowl known to be intermediate hosts

2. Control of mosquitoes is major countermeasure.

B. Yellow Fever: Live attenuated virus vaccine. Used when going to endemic areas

/ If we have break any of these (host ,virus ,vector) so you prevent the cycle of infection .

Arboviruses

Positive sense ssRNA genome, icosahedralnucleocapsid, enveloped
Pathogenesis / Structure
Transmitted by bite of insect from host species; sylvan and urban cycles
Replication in cytoplasm; budding
Viremia to target tissue
Influenza-like initial symptoms; different viruses cause encephalitis, hemorrhagic fever, hepatitis, rash, arthritis / Pathogenesis
Serology and nucleic acid / Diagnosis
No human vaccines except for Yellow Fever live attenuated vaccine, control of insect population / Treatment/prevention

GENERAL HISTORY OF RETRO VIRUS

1960: The name of retroviruses came from Howard Temin who is the first one discovered the( reverse transferees) in bacteria and has the nobal prize in 1990.

1980: Human T-cell leukemia virus discovered, the first pathogenic human retrovirus.

1982: Human immunodeficiency virus discovered, But actually it is not discovered at that time but the up normal clinical picture it was seen at that time

1990: First gene therapy trial involving the use of retroviral-based vectors (they take the gene responsible for production ADA and attach it with the RNA of retrovirusand inject it in the host cell )which is a patient with a deficiency in adenosine deaminase (ADA)so he well be able to produce it

2006: Xenotropicmurine leukemia-related virus discovered.

Retroviruses

Retro virus from it is name it is ( DNA….RNA…Protein) virus.

Unique replication cycle based on reverse transcription;Flow of information from RNA to DNA

Retrovirusescause tumor to their original host cell&they have been isolated from numerous speciesincludingchickens (RSV), mice (MLV), monkeys (SIV), and humans (HIV, HTLV).

Type of retrovirus

*Simple Retroviruses: it contain at least 3 main gen group which needed for synthesize virus.(we well talk about it ).

*Complex retrovirus: composed of 3 gen found in simple virus in addition to anther gen

How theyinfect the cell ??

Reteovirusenvelope so it has to attach to the membrane receptor of the host cell and they enter to the cell and infect it .

One IMP thing about it :we know in Tumor production we have something called oncogen.

Oncogenfirst timediscovered in retroviruses and these virus sometime we call it retrovirus oncogen..(if mutation occur in the original virus they become oncogen and cause tumor viruses )

THE OLD NOMENCLATURE//Members(groups):

1-Oncogenic viruses (Oncoviruses) (endogenous)

Avian oncoviruses: RSV, AMV, AEV

Murineoncoviruses: e.g.,MoMLV, A-MuLV.

Mammalian oncoviruses: e.g., FeLV, HaMSV, SSV .

Mouse Mammary Tumor Virus (MMTV)

Mason-Pfizer Monkey Virus (MPMV

Human T-Cell Lymph tropic Virus

2-Lentiviruses– HIV-1, HIV-2(associated with “slow” diseases or thosewith long latent periods)

3-Spumaviruses – mainly in monkey(“foamy” viruses named because of the pathogenic change observed I infected cell )

Slide 50: dr mentionone example on

simple virus:Alpharetrovirus( Avian leukemia virus )

And complex virus :Deltaretrovirus(Human T-cell leukemia virus)

General feature for retrovirus

1-Enveloped virus with lipid bilayer and viral spike glycoproteins

2-Have outer matrix protein and inner core capsidcontaining viral genome

3-Genome: Two copies of singlestranded positive-stranded(+ RNA)

4-All retroviruses containgag, pol and envgenes.

5-Simple –only gag, pol, env,Complex–additional genes involved in replication

6-All of them have Reverse transcriptase to generate DNA

7-Viralgenes are integrated into host genome.

8-Progeny virus producedusing host cell transcriptional and translational machinerywhich meen it well stop the cellular function of the host cell and turn it to viral ccc.

Retrovirus Genome (Diploid)

Retrovirus genome is +RNA ,Ranges from 7-10 kb in size (1 copy)Diploid: 2 copies/virion,Important in high recombination rateSo their antigencty not stable &always there is change.

This gag(group spasificantigen,pol(polymerase enzyme), env(envelope) ) gene of simple virus

In complex we can add another gen :

MA-Matrix, CA- Capsid , NC- Nucleocapsid

In other we can add :

SU- surface envelope protein, TM- transmembrane envelope protein

in addition it can produce :

PRO- Protease, RT- Reverse transcriptase ,IN- Integrase

Viral life cycles

There is :

Virulent – these viruses lyse (kill) their host cell after infection.RapidTemperate – these viruses can replicate their genome along with the host cell genome without killing the host cell.but if anything activated the cell the virus start to develop very rapidly it can be induced by IL,infection,drug And capable oflyzing the host cell.need along time

Distinct Steps in the Retroviral Life Cycle/look to 1icture

1st step :Attachment, Fusion, and Entry

2nd step :Reverse Transcription

3rd step :Integration

4th step:Transcription

5th step:Translation

6th step :Assembly, Budding, and Maturation

DONE BY JUMANA MANSOUR AL-ZOUBI

BEST OF LUCK

SORRY FOR AN ANY MISTACKES

SPECIAL THANX TO MY SISTER NARIMAN